Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (<i>SHC3</i>) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of <i>SHC3</i> and schizophrenia.Methods An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population.Results The allelic and genotypic association analyses showed that four SNPs in <i>SHC3</i> significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia.Conclusion Our present results suggest <i>SHC3</i> as a susceptibility gene for schizophrenia.
Abstract
Objective Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (<i>SHC3</i>) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of <i>SHC3</i> and schizophrenia.Methods An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population.Results The allelic and genotypic association analyses showed that four SNPs in <i>SHC3</i> significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia.Conclusion Our present results suggest <i>SHC3</i> as a susceptibility gene for schizophrenia.
참고문헌 (27)
- Saha S, "A systematic review of the prevalence of schizophrenia", PLoS Med, 2, pp.e141~ (2005)
- Tandon R, "Schizophrenia, “just the facts”what we know in 2008. 2. Epidemiology and etiology", Schizophr Res, 102, pp.1~18 (2008)
- Ross CA, "Neurobiology of schizophrenia", Neuron, 52, pp.139~153 (2006)
- Cardno AG, "Heritability estimates for psychotic disorders : the Maudsley twin psychosis series", Arch Gen Psychiatry, 56, pp.162~168 (1999)
- International Schizophrenia Consortium, "Common polygenic variation contributes to risk of schizophrenia and bipolar disorder", Nature, 460, pp.748~752 (2009)
- O’Bryan JP, "A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosinebinding domains is related to Shc and is specifically expressed in the brain", Proc Natl Acad Sci U S A, 93, pp.2729~2734 (1996)
- Ponti G, "Comparative expression profiles of ShcB and ShcC phosphotyrosine adapter molecules in the adult brain", Neuroscience, 133, pp.105~115 (2005)
- Triaca V, "NGF controls APP cleavage by downregulating APP phosphorylation at Thr668 : relevance for Alzheimer’s disease", Aging Cell, 15, pp.661~672 (2016)
- Gong J, "Lentiviral Vector-Mediated SHC3 silencing exacerbates oxidative stress injury in nigral dopamine neurons by regulating the PI3K-AKT-FoxO signaling pathway in rats with Parkinson’s disease", Cell Physiol Biochem, 49, pp.971~984 (2018)
- Xie Z, "RNA interference silencing of the adaptor molecules ShcC and Fe65 differentially affect amyloid precursor protein processing and Abeta generation", J Biol Chem, 282, pp.4318~4325 (2007)
- Tarr PE, "Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc", J Biol Chem, 277, pp.16798~16804 (2002)
- Miyamoto Y, "Hippocampal synaptic modulation by the phosphotyrosine adapter protein ShcC", N-Shc via interaction with the NMDA receptor, 2005, pp.25, 1826~1835
- Magrassi L, "EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas", Cancer Lett, 290, pp.36~42 (2010)
- Miyake I, "Distinct role of ShcC docking protein in the differentiation of neuroblastoma", Oncogene, 28, pp.662~673 (2009)
- Magrassi L, "Shc3 affects human high-grade astrocytomas survival", Oncogene, 24, pp.5198~5206 (2005)
- Conti L, "Shc signaling in differentiating neural progenitor cells", Nature Neurosci, 4, pp.597~586 (2001)
- Wong J, "Increases in two truncated TrkB isoforms in the prefrontal cortex of people with schizophrenia", Schizophr Bull, 39, pp.130~140 (2013)
- American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders" (2000), American Psychiatric Publishing
- Barrett JC, "Haploview : analysis and visualization of LD and haplotype maps", Bioinformatics, 21, pp.263~265 (2005)
- Shi YY, "SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci", Cell Res, 15, pp.97~98 (2005)
- Li Z, "A partition-ligationcombination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http:", Cell Res, pp.2009, 19[DOI]
- Marder SR, "Schizophrenia", N Engl J Med, 381, pp.1753~1761 (2019)
- Ortensi B, "Rai is a new regulator of neural progenitor migration and glioblastoma invasion", Stem Cells, 30, pp.817~832 (2012)
- Finetti F SM, "Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters", Inmmun Rev, 232, pp.115~134 (2009)
- Azzalin A, "Cell density modulates SHC3 expression and survival of human glioblastoma cells through Fak activation", J Neurooncol, 120, pp.245~256 (2014)
- Baba S, "Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity", Sci Rep, 6, pp.27511~ (2016)
- Meary A, "A Snap25 promoter variant is associated with schizophrenia and a disturbed Snap25b", Snap25a expression ratio in patients, 2010, pp.117, 449~450